The development and progression of cancer places a significant emotional and financial burden on society.
Bladder cancer is the second most common genitourinary tumour in human populations, with an incidence of approximately 261,000 new cases each year worldwide; about a third of those are likely to be invasive or metastatic disease at the time of diagnosis (Parkin et al., 1999).
As with many other cancers, clinical diagnosis of bladder cancer can be a difficult process, particularly in the early stages of cancer development. At present, cystoscopy and urine cytology are the most important tools in the diagnosis and follow-up of bladder cancer.
At present, cystoscopy with biopsy is generally considered the gold standard for diagnosing bladder cancer. A drawback to using cystoscopy is that it requires an invasive procedure. In addition to being invasive, obtaining a biopsy via cystoscopy can have potential adverse outcomes for the patient. Given these limitations, it is very difficult to obtain patient samples via cystoscopy, repeatedly from a large number of individuals.
Accordingly, clinicians generally rely on routine cytology to identify patients at risk of developing bladder cancer prior to cystoscopy. Routine cytology suffers from two well accepted limitations that reduce its utility as a diagnostic tool for early stage cancer.
First, cytology has poor sensitivity for low grade cancer. Accordingly, routine cytology returns a high level of false-negative results in low-grade cancer samples that completely lack cellular morphological abnormalities. Second, the usefulness of cytology for the detection of low grade disease, or hard to diagnose lesions, is limited. For example, when using cytology for the diagnosis of bladder cancer, a large proportion of cases (20-25%) are reported as atypical, including “atypical urothelial cells of unknown significance” (AUCUS) and “atypical urothelial cells, cannot exclude high-grade urothelial carcinoma (AUHGC)” (Rosenthal et al., 2013). A reported outcome of AUCUS or AUHGC is of little or no diagnostic utility.
A need therefore exists for a method capable of providing a more accurate, early and economically viable diagnosis of cancers. Such a method could provide assistance to clinicians in reaching an early stage diagnosis prior to the portrayal of detectable morphological indicators. Moreover, early diagnosis of cancer, prior to invasion and metastasis, is generally associated with improved prognosis. Accordingly, there is a social and economic imperative to provide a method that can more reliably detect cancer at an early stage, so anti-cancer therapy can be administered at a time when the disease burden is mild.